Various Nickel compounds with different carcinogenic activities in experimental animals will be tested for their activity to induce morphological transformation in tissue culture. Selected morphologically transformed colonies induced by exposure of cells to metals will be cloned and tested for their ability to proliferate in soft agar and induce tumors in Nude Mice. Mutagenic activity of the various Nickel compounds will also be examined using a mammalian cell culture system. The striking differences in uptake between the carcinogen Ni3S2 and the non-carcinogen amorphous NiS suggests that this phenomena may explain why specific metal compounds have different carcinogenic activities. We will therefore study the uptake of various Nickel compounds using light and electron microscopy and correlate this with their carcinogenic activity. We will also compare the subcellular distribution of Nickel in cultures that have been treated with amorphous NiS and crystalline Ni3S2. Nickel levels in various subcellular fractions will be measured by X-ray fluorescence. The differences in the inducibility of ornithine decarboxylase will also be studied in normal and Ni3S2 transformed Syrian hamster embryo cells.